Study: Flu, fever in pregnancy linked to autism risk

In a study that's already being greeted with notes of caution, Danish researchers report that children whose mothers had the flu or ran a fever lasting more than a week during pregnancy had an increased risk of developing an autism spectrum disorder.

U.S. health officials stress that the new study, out in today's Pediatrics, is "exploratory" and does not offer a specific cause of the developmental disability.

The study analyzed data collected from 97,000 mothers of children born from 1997 through 2003. It found no association between mothers who reported common respiratory or sinus infections, common colds, urinary tract or genital infections, during pregnancy and autism in their offspring.

But children whose mothers reported influenza during pregnancy had twice the risk of being diagnosed with autism before age 3, and children whose mothers had a fever for more than seven days had a threefold risk.

There was also a small increased risk of autism after the mother's use of various antibiotics during pregnancy. The study did not specify the conditions for which the antibiotics were prescribed.

"The study is really exploratory, and more research needs to be done to understand how maternal infections, as well as other risk factors, influence the risk of autism spectrum disorders," says Coleen Boyle, director of the Centers for Disease Control and Prevention's National Center on Birth Defects and Developmental Disabilities. "We need to have more information to get a better sense of what's going on here."

Autism researcher Irva Hertz-Picciotto, a professor of environmental epidemiology at the University of California-Davis MIND Institute who was not involved in the new study, says that the findings are "noteworthy," especially given the study's size and that the mothers were interviewed during and shortly after pregnancy, and did not know what the child's outcome would eventually be, thereby eliminating "recall bias."

In May, Hertz-Picciotto co-authored a study in the Journal of Autism and Developmental Disorders that found fever during pregnancy more than doubled the risk of autism or developmental delay in children. Flu during pregnancy, however, was not associated with a greater risk.

"Mothers who reported a fever and reported not taking any medication to reduce fever were at higher risk to deliver a child that later developed autism. On the other hand, if they had a fever and took a medication to reduce fever, their child was not at higher risk," Hertz-Picciotto said in an e-mail.

Fever is produced by acute inflammation - the short-term, natural immune system reaction to infection or injury, she says. Both her study and the new study raise the question whether inflammation may play some role in causing autism, says Hertz-Picciotto. Neither study proves causation, she says, "but add to the literature on fever and on infection."

Boyle says that the new study is "one piece of that very large ... very important puzzle to figuring out autism." Findings from CDC's Study to Explore Early Development (SEED), initial publication is expected in 2013, will provide additional information, she says.

For now, the standard clinical recommendations for treating pregnant women suffering from fever or flu should not change as a result of the new preliminary findings, says Marshalyn Yeargin-Allsopp, chief of CDC's Developmental

Disabilities Branch. "We don't want women to not take antibiotics or not treat fever if they have the flu," she says.

Other adverse health affects, such as structural malformations resulting in birth defects, have been associated with fever in pregnancy, says Boyle, "so there are other reasons to treat fever besides the findings from this new research."

Likewise, flu shots are critically important for pregnant women, "both because pregnant women are more likely to develop severe disease compared to non-pregnant women, but because there can also be effects on the baby," says Denise Jamieson, chief of CDC's Women's Health and Fertility Branch.

"Getting a flu shot while you're pregnant protects your baby for up to six months of life," a period when babies are too young to be immunized, she adds: "So it's good protection for the mom and good protection for the baby."